<br>姜黄素通过ATF6介导的内质网应激影响结直肠癌细胞凋亡,Chemical Biology & Drug Design

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姜黄素通过ATF6介导的内质网应激影响结直肠癌细胞凋亡
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2024-01-04 , DOI: 10.1111/cbdd.14433
Wei Xu ₁ , Yu Shen ₂

Affiliation

结直肠癌（CRC）是癌症相关死亡的主要原因。在此，我们用不同浓度的姜黄素处理 SW620 和 HT-29 CRC 细胞，然后用半数抑制浓度 (IC50) 姜黄素/内质网应激 (ERS) 抑制剂 4-苯基丁酸 (4-PBA)/激活转录处理因子 6 (ATF6) 干扰质粒 (si-ATF6)。我们检测了细胞增殖/凋亡、ATF6 细胞定位/核转位、离子浓度、ATF6 蛋白/凋亡蛋白 (Bax/Bcl-2/Cleaved Caspase-3) 水平和 ERS 相关蛋白（葡萄糖调节蛋白 78 [Grp78]） /C/EBP 同源蛋白 [CHOP])。我们发现细胞增殖/生长受到抑制，细胞凋亡/(Bax/Bcl-2)比率/Cleaved Caspase-3水平/细胞质中的Ca ²⁺浓度/ERS相关蛋白(Grp78/CHOP)水平增强，并在以下情况下激活ERS用IC50姜黄素治疗。 4-PBA通过抑制ERS，部分逆转了姜黄素对SW620细胞的抑制作用。姜黄素刺激 ATF6 表达及其核转位以激活 ERS。 ATF6 沉默部分抵消了姜黄素对 SW620 细胞的抑制作用。我们的研究探讨了姜黄素通过ATF6影响CRC细胞凋亡的分子机制。

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Curcumin affects apoptosis of colorectal cancer cells through ATF6-mediated endoplasmic reticulum stress

Colorectal cancer (CRC) is the main cause of cancer-associated death. Herein, we treated SW620 and HT-29 CRC cells with different curcumin concentrations, followed by treatment with the half maximal inhibitory concentration (IC50) curcumin/endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid (4-PBA)/activating transcription factor 6 (ATF6) interference plasmid (si-ATF6). We detected cell proliferation/apoptosis, ATF6 cellular localization/nuclear translocation, ion concentration, ATF6 protein/apoptotic protein (Bax/Bcl-2/Cleaved Caspase-3) levels, and ERS-related proteins (glucose-regulated protein 78 [Grp78]/C/EBP homologous protein [CHOP]). We discovered inhibited cell proliferation/growth, enhanced cell apoptosis/(Bax/Bcl-2) ratio/Cleaved Caspase-3 levels/Ca²⁺ concentration in the cytoplasm/ERS-related protein (Grp78/CHOP) levels, and activated ERS following treatment with IC50 curcumin. 4-PBA partially reversed the inhibitory effect of curcumin on SW620 cells by restraining ERS. Curcumin stimulated ATF6 expression and its nuclear translocation to activate ERS. ATF6 silencing partly annulled the inhibitory effect of curcumin on SW620 cells. Our study explored the molecular mechanism of curcumin affecting CRC cell apoptosis through ATF6.

更新日期：2024-01-06

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